The National Strategic Research Institute at the University of Nebraska recently highlighted the capabilities within UNMC’s Multiomics Mass Spectrometry Core as the NSRI feature university facilities and centers that can directly contribute to NSRI’s mission.
The potential threat of unknown or unexpected chemical or biological agents, whether weaponized or naturally occurring, is one of the most concerning defense problems the U.S. faces. Even known agents can present an immense threat to the safety and security of the Nation and its warfighters.
To understand how to potentially prevent these agents from causing harm, it is essential to understand exactly how various chemical and biological agents can affect the human body at the subcellular level, including changes in proteins and metabolites.
The Multiomics Mass Spectrometry Core facility at UNMC is uniquely equipped to advance this understanding. It is home to over $10 million in state-of-the-art robotics equipment and mass spectrometry instrumentation that are used by some of the most talented researchers in the field who execute highly optimized and automated processes to obtain fast, accurate answers.
“Leveraging omics is a key part to any new drug development project for the Department of Defense (DOD),” said Terry Thiem, PhD, director for medical countermeasures at the National Strategic Research Institute at the University of Nebraska. “The information proteomics provides helps uncover post-translational modifications to proteins, which is key to deciphering disease mechanisms and mechanisms of action for drug development. Metabolomics is equally valuable to drug development when assessing drug metabolism and toxicity as well as identifying biomarkers associated with diseases.”
About the Multiomics Mass Spectrometry Core
Established in 2007, the facility provides sample preparation equipment, mass spectrometry instrumentation, bioinformatics tools and expertise to support projects for both UNMC researchers and outside clients. The lab’s proven workflows and technology uncover perturbations in biological processes, which allows researchers to define and understand the effects of harmful agents, pointing the researchers in the right direction to develop drugs and treatments to mitigate the damage that might be caused when such agents are encountered across the world.
“What we do is applicable to any biological question or disease,” said Rebekah Gundry, PhD, the facility’s scientific director and an internationally recognized expert in mass spectrometry. “Cancer, heart disease, biological warfare, chemical warfare — all those areas of research can benefit from understanding what’s happening at the molecular level.”
Unlike other technologies that focus on selected analytes, mass spectrometry does not require prior knowledge of exactly what to look for. Mass spectrometry uses inherent information about a molecule to identify and characterize it, which makes it a perfect technology for understanding new biological agents, among other applications.
Already an asset to UNMC researchers for these strengths, the facility underwent a major overhaul in 2024 to bring it in line with cutting-edge developments in the field. In the past year, the facility has continually streamlined its processes to provide the most efficient and accurate readings possible, making it a first-choice facility for many in biomedical research. The core now features highly streamlined and robotic-driven sample preparation processes that allow the lab to process hundreds or even thousands of samples in a day. Dr. Gundry said the robotics equipment for sample preparation is one of the more unique things about the facility.
“By automating the sample preparation process, we no longer rely on investigators to prepare their own samples, which historically has led to a high failure rate unless the person preparing them is an expert in mass spectrometry,” she said.
Automation makes it easier for the core lab to prepare high throughput sample numbers with limited staff and offers the advantage of a more controlled, more reproducible process.
Dr. Gundry explained: “We need less starting material than we would if we did all the preparation manually. Our sample quantities needed are also lower due to the enhanced sensitivity of our state-of-the-art mass spectrometry instrumentation. This increased sensitivity means the data quality is better, and we can analyze more rare cell populations or samples with more limited availability. Also, by freeing up staff time for other tasks and ensuring high success rates, this also leads to cost savings that we can pass along to our users.”
The Multiomics Mass Spectrometry Core also installed new state-of-the-art mass spectrometry instrumentation and bioinformatic tools in 2024.
Key to the UNMC facility’s success, the top-of-the-line instrumentation allows for more detail than has been achievable in the past.
“Our new instrument offers unprecedented sensitivity and capabilities for a wide variety of molecule types such as proteins, glycans and lipids,” Dr. Gundry said. “And our personnel have the experience to make that work — we boast an expertise in a wide range of molecule types — both common and uncommon.”
Thermo Orbitrap Astral™ Mass Spectrometer
This top-of-the-line instrument is among the most advanced and high-throughput mass spectrometers available and is applicable to any area of biological science. It can be used to analyze nearly any molecule type there is — and does so with minimal sample load requirements.
Thermo Orbitrap Exploris™ 480 Mass Spectrometer – System 1
Primarily used for untargeted proteomics, this instrument enables researchers to rapidly perform discovery-based analyses to identify changes in thousands of protein modifications or protein abundances across samples in under 30 minutes per sample. In doing so, researchers can gain a wide range of insights regarding how treatment affects the molecular landscape of the cell, tissue or fluid.
Thermo Orbitrap Exploris™ 480 Mass Spectrometer – System 2
Mostly used for untargeted metabolomics, this instrument allows researchers to quantify thousands of metabolites, lipids or small molecules in a single run. Researchers can use this information to understand the biochemical activity of a cell or system, including how they are adapting to toxins or stress.
Sciex QTRAP® 5500 Mass Spectrometer
This instrument is used for targeted quantification of metabolites, lipids and small molecules and allows researchers to dig deep into specific changes across samples through absolute quantitation. While other systems are most commonly programmed to provide relative abundance, this instrument can provide precise concentrations of a particular target — for example, it can be used to determine how much alcohol is in a person’s bloodstream, even if it’s metabolized in an unusual way.
Opentrons® OT-2 Liquid Handler
The backbone of the facility’s efficient throughput, these robots are specifically designed to quickly prepare samples using simple and complex workflows with higher precision and accuracy with less starting material than those prepared by humans.
Tecan Resolvex® A200 Positive Pressure Workstation
This robotic workhorse is the first step for most proteomic and glycomic workflows in the core lab and is used in conjunction with the Opentrons systems, enabling fully automated processing from start to finish.
Experienced experts
The Multiomics Mass Spectrometry Core facility supports a broad range of researchers, students and other stakeholders. Dr. Gundry and manager Melinda Wojtkiewicz, principal operators of the lab, contribute highly advanced skills and expertise to all projects.
Rebekah Gundry, PhD
A well-respected researcher in her field and recipient of numerous awards, Dr. Gundry has used mass spectrometry for more than 20 years, since earning her doctorate in pharmacology and molecular medicine from Johns Hopkins University School of Medicine. As research director of the facility, Dr. Gundry ensures that the core remains at the leading edge, providing technologies essential to driving biomedical research.
Melinda Wojtkiewicz
Wojtkiewicz brings more than 20 years of experience in both industry and academia, developing and applying mass spectrometry technologies to analyze all types of biological molecules. Wojtkiewicz is the facility’s manager and is the driving force behind the ever-improving automated workflows that lead to the impressive efficiency and accuracy the lab is known for.
Contributions to American defenders
With very few labs in the country harnessing the technology and expertise to operate as quickly and precisely as war theater conditions demand, it is not a surprise that the Multiomics Mass Spectrometry lab already has been used for a number of projects that directly benefit warfighters.
One DOD-funded project involves developing methods to help soldiers who have been exposed to high levels of radiation and have developed acute radiation syndrome (ARS). Dr. Gundry and her team recently applied their technologies to identify and quantify more than 7,000 proteins in a sample treated with the experimental countermeasure.
“We looked at what happens to the bone marrow when it is exposed to radiation, and we are investigating the effects of specific countermeasures,” Dr. Gundry said. “We want to understand how the countermeasures help the bone marrow, and the rest of the body, preserve themselves from radiation damage.”
The key benefit of mass spectrometry in this type of research is being able to discover exactly how toxins, medicines and microorganisms interact with the human body at the molecular level. That level of insight is invaluable for identification, prevention and treatment of diseases and other threats to warfighters, not to mention any suffering patient.
“When something bad happens to someone — for example, if they’re having trouble breathing — that doesn’t give us a target to go after when we want to develop a drug or therapy,” Dr. Gundry said. “Understanding a person’s behavior and physiology is important, but we need to understand what’s happening at the level of proteins, sugars, metabolites and lipids.
“Those molecules are doing things to sustain normal cellular and organ function. When something happens to the molecules, it can change what they’re interacting with, their location, etcetera. Those basic principles guide our understanding of diseases and the development of treatments.”
The health and safety of warfighters also benefit from mass spectrometry when it is used to identify biomarkers of exposure to a particular chemical, toxin, disease or virus. By identifying those biomarkers, healthcare workers can more accurately scan for what an individual might have been exposed to. That means they can get treatment faster, rather than waiting until the person has devastating, outwardly visible effects or internal symptoms.
“It’s nice to have those biomarkers available to allow us to detect disease processes earlier and predict outcomes,” Dr. Gundry said.
An ever-evolving, efficient process
The benefit of using the Multiomics Mass Spectrometry Core doesn’t stop with the facility’s cutting-edge technology, automation, data analytics and talented and experienced staff who are committed to ensuring the projects deliver accurate results. The lab also offers a unique depth and adaptability of its processes and expertise.
Every project at the facility begins with a free consultation with Dr. Gundry and Melinda Wojtkiewicz, who work with the client to develop a full design for the project, as well as an estimated timeline and budget.
“We go to great lengths to ensure we define exactly what the goal of each project is, what samples are needed, what workflows and instrumentation are appropriate, and what clients can expect from us,” Wojtkiewicz said. “At the end of the project, we provide an extensive report that goes through step-by-step what we’re checking for quality control, what the data look like for each run and other important metrics.
“We can help you dig into the data — and if we can’t help, we probably know someone who can.”
Cross-field benefits of mass spectrometry
Mass spectrometry is a key process for innumerable projects in chemical and biological fields. The incredible advancements made in medicine would not be possible without extensive information — and mass spectrometry provides some of the most detailed and precise information imaginable.
No matter what the chemical and biological threats of the future bring, detailed information is essential to understanding and ultimately combating them.
The UNMC Multiomics Mass Spectrometry Core facility is working tirelessly to push the foundations of medical research and hone its own processes to help ensure the United States is ready to rapidly react to the next threat to the nation’s well-being.